Impact of factor VIII deficiency on clotting factor utilization in the United States

Summary In a study of 1,551 hemophiliacs over a 4-year period of time, factor VIII utilization was assessed. It is clear that factor VIII usage is a function of severity of disease and therapeutic program. The average amount of factor VIII used per patient was 39.880U/year. Patients seiected for home care, use significantly more than those patients not on home care. As much as 101,000 U/year are used by a small number of patients on prophylaxis. These data can be used in predicting source plasma requirements for annual national use as well as costs. National Heart, Lung and Blood Insititute Cooperative Study of Spontaneously Occurring Factor VIII Inhibitors in Hemophilia Work supported under contracts (1-HB-5-3016 through 3025 cooperating centers and 1-HB-5-3035 reference laboratory and coordinating center) with the National Heart, Lung and Blood Institute and by^*HSA grant #MCB-360001-04-01, Regional Comprehensive Hemophilia Diagnostic and Treatment Center, The Margie Boas Fund, International Hemophilia Training Center of the World Federation of Hemophilia, Polly Annenberg Levee Hematology Center, Department of Medicine, Mount Sinai School of Medicine of the City University of New York, N.Y. 10029.     

内皮祖细胞内皮修复的影响因素

内皮祖细胞（EPC）来源于骨髓,能够定向分化为成熟有功能的血管内皮细胞,是血管内皮细胞的前体细胞,又称血管母细胞。内皮祖细胞在组织缺血和血管损伤时动员入血,促进微血管的生成和血管内皮的修复,不仅参与胚胎血管生成,也参与出生后的血管发生过程,具有保护血管内皮、减少心血管疾病的发生率和死亡率的作用。许多试验证实冠状动脉粥样硬化性心脏病（冠心病）和心力衰竭患者EPC数量减少,外周循环内皮细胞功能受损。研究发现,EPC的生物学特性受到诸多冠心病危险因素的影响,致使其功能异常。     

Laboratory testing in hemophilia: Impact of factor and non‐factor replacement therapy on coagulation assays

The advent of extended half‐life (EHL) recombinant clotting factors and innovative non‐factor replacement therapeutics, such as emicizumab, offers several advantages over existing products for the prophylactic treatment of people living with hemophilia (PwH). These include low annual bleeding rates with less frequent dosing, higher trough plasma concentrations, and a more convenient route of administration. However, increasing use of these therapies poses challenges to clinicians and coagulation laboratories due to the lack of standardized assays for monitoring of hemostatic parameters, and the potential for misinterpretation of test results, which may jeopardize patient safety. Definitive diagnosis of hemophilia and treatment monitoring is reliant on demonstrating factor VIII (FVIII; hemophilia A) or factor IX (FIX; hemophilia B) deficiency using a functional coagulation assay. The most frequently used assays are based on activated partial thromboplastin time, using a one‐stage or two‐stage process. While one‐stage and chromogenic assays have performed well with human‐derived FVIII and FIX and full‐length recombinant products, EHL recombinant factors are heterogeneous in structure and mode of action and therefore show wide variation in activity levels between different one‐stage assays, and between one‐stage and chromogenic assays. In the context of the recommended stepwise approach for laboratory diagnosis of hemophilia, we examine the diagnostic challenges associated with the use of EHL factors and novel non‐factor therapeutics and consider the optimal diagnostic approach in PwH who are receiving these treatments. Ultimately, accurate diagnostic solutions are a prerequisite for personalized therapy to minimize treatment burden and improve quality of life in PwH.     

神经生长因子对缺氧缺血性脑损伤细胞凋亡的影响

背景:细胞凋亡是脑缺氧缺血神经细胞死亡的一种方式,体外试验表明神经生长因子(nervegrowthfactor,NGF)缺乏可诱导神经细胞凋亡。目的:探讨新生儿缺氧缺血性脑损伤(hypoxic-ischemicbraindamageHIBD)与细胞凋亡之间的关系,研究NGF对HIBD的保护作用,为用NGF治疗新生儿HIBD提供理论依据。设计:完全随机设计,对照实验研究。地点与材料:7dSD大鼠40只来源于南京医科大学实验动物中心,体质量约14～18g,雌雄不拘,饲养于屏障环境的SPF级实验动物。干预:40只大鼠制成HIBD动物模型,随机分成两组:HIBD模型对照组20只,NGF治疗组在大鼠缺氧缺血后即刻腹腔注射NGF。主要观察指标:观察NGF对HIBD模型的新生大鼠体质量增长情况、死亡率、左右脑质量影响,并用原位缺口末梢标记(insitunickendlabeling,TUNEL)法检测NGF对缺氧缺血后脑细胞凋亡的影响。结果:HIBD模型NGF治疗组体质量增长明显高于对照组(P<0.01);治疗组实验过程中死亡率明显低于对照组;HIBD模型NGF治疗组与对照组健侧(右侧)脑质量相近,但治疗组患侧(左侧)脑质量犤(0.57±0.02)g犦明显重与对照组犤(0.42±0.1)g,P<0.01犦;治疗组左右脑质量无显著差异,而对照组左右脑质量差异有显著性意义(P<0.01);TUNEL染色所见阳性凋亡细胞,其凋亡特征为胞体缩小、核固缩、核碎     

Impact of platelet activating factor on vascular responsiveness in isolated rat lungs

Platelet activating factor (PAF), a suspected mediator of acute lung injury, has been shown to potentiate contraction in isolated porcine carotid arteries. Such an action of PAF, if it occurred in the pulmonary circulation, could be of significance to the evolution of pulmonary hypertension in acute lung injury. Accordingly, we used isolated rat lungs perfused at a constant flow rate with physiologic salt solution to test the hypothesis that PAF-induced lung injury is associated with pulmonary vascular hyperresponsiveness to constrictor stimuli. PAF in concentrations of 0.1 to 10 ng/ml failed to influence pressor responses evoked by i.a. bolus injections of angiotensin II (Ang II) whereas 1 micrograms/ml of PAF significantly blunted Ang II-induced vasoconstriction. Similarly, 1 micrograms/ml, but not 0.1 ng/ml, of PAF attenuated constriction induced by ventilation with 3% O2. PAF at all concentrations tested failed to influence pressor responses evoked by i.a. bolus injections of KCI. Concentrations of PAF which blunted Ang II and hypoxic responses were associated with increased lung wet-to-dry weight ratios indicative of pulmonary edema. Another agent that provokes edema, cytochalasin B, also increased lung wet-to-dry weight ratios and blunted Ang II-, hypoxia-, and KCI-induced pressor responses. PAF delivered as i.a. bolus injections caused acute vasodilation in preparations preconstricted with Ang II but not in those preconstricted with KCI. Collectively, these observations demonstrate that PAF fails to augment and instead blunts pulmonary vascular responsiveness to pressor stimuli, possibly by mechanisms that relate to PAF-induced edema formation and/or vasodilation.     

Impact of cytomegalovirus infection on biliary disease after liver transplantation - maybe an essential factor

BACKGROUNDCytomegalovirus (CMV) infection is common in liver transplant (LT)_ recipients, and biliary complications occur in a large number of patients. It has been reported that CMV-DNA is more detectable in bile than in blood.AIMTo investigate the effects of CMV infection on biliary complications by comparing the levels of CMV-DNA in the bile and blood of patients after LT.METHODSWe conducted a retrospective analysis of 57 patients who underwent LT, 10 of these patients had no biliary complications and 47 patients had biliary complications. We also compared the levels of CMV-DNA in patients’ bile and blood, which were sampled concurrently. We used RNAscope technology to identify CMV in paraffin-embedded liver sections.RESULTSCMV-DNA was not detected in bile samples and was detected in 2 blood samples from patients without biliary complications. In the 47 patients with biliary complications, CMV-DNA was detected in 22 bile samples and 8 blood samples, both bile and blood samples were positive for CMV-DNA in 6 patients. The identification rate of CMV-DNA in blood was 17.0%, and was 46.8% in bile. Moreover, tissue samples from 4 patients with biliary complications tested positive using RNAscope technology but were negative with hematoxylin and eosin staining. During the follow-up period, graft failure occurred in 13 patients with biliary complications, 8 of whom underwent retransplantation, and 3 died. CMV-DNA in bile was detected in 9 of 13 patients with graft failure.CONCLUSIONIn patients with biliary complications, the identification rate of CMV-DNA in bile was higher than that in blood. Blood CMV-DNA negative patients with biliary complications should still be monitored for CMV-related biliary tract diseases. Potential occult CMV infection may also be a contributing etiological factor in the development of graft failure.     

神经生长因子对缺氧缺血性脑损伤患者闪光视觉诱发电位的影响

背景闪光视觉诱发电位(flash-visual evoked potential,F-VEP)是目前儿科临床评估中枢神经系统功能状态的一项新的易行方法.目的探讨闪光视觉诱发电位(F-VEP),反映新生大鼠缺氧缺血性脑损伤(hypoxic-ischemic brain damage,HIBD)的敏感性,研究神经生长因子(nerve growthfactor,NGF)对新生鼠缺氧缺血性脑损伤的保护作用,为新生儿HIBD的早期诊断与干预提供理论依据.设计完全随机设计,对照实验研究.地点与材料研究地点为南京医科大学第二附属医院儿科,生后7 d SD大鼠来源于南京医科大学实验动物中心,共60只,体质量约14～18 g,雌雄不拘,饲养于屏障环境的SPF级实验动物.干预40只大鼠制成HIBD动物模型后随机分成两组HIBD模型未治疗组20只,HIBD模型NGF治疗组20只,另20只为正常对照组.主要观察指标观察正常对照组及HIBD后F-VEP改变;NGF对HIBD模型的新生大鼠体质量增长情况、死亡率、左右脑质量及F-VEP波形影响.结果HIBD模型NGF治疗组体质量增长(11.9±3.5)g,实验过程中死亡率为5%,患侧(左侧)脑质量(0.59±0.02)与未治疗组相比差异有显著意义(P均＜0.01);治疗组左右脑重量差异无显著意义,而未治疗组左右脑质量[(0.39±0.10)g,(0.57±0.05)g]差异的显著性意义(P＜0.01);HIBD后NGF治疗组与未治疗组即刻F-VEP潜伏期[(36.84±2.120)ms,(36.44±1.94)m]均较对照组(30.27±1.52)m明显延长(P＜0.01),波幅降低(P＜0.01);NGF未治疗组7d后与同期对照组相比F-VEP潜伏期[(48.17±2.08)m,(29.80±1.93)ms]明显延长,波幅降低[(3.75±0.69)mV,(4.22±0.87)mV](P均＜0.01);同期NGF治疗组与未治疗组相比F-VEP潜伏期(32.08±1.85,48.17±2.08)明显缩短,波幅升高[(3.97±0.75)mV,(2.75±0.69)mV,P均＜0.01].结论F-VEP主波潜伏期、波幅可较迅速反映HIBD后脑功能状态;NGF治疗减轻了HIBD后脑萎缩、改善了脑功能.     

高血压患者门诊药物治疗血压达标的影响因素

目的 了解现实治疗状况中,对高血压患者在门诊药物治疗中,影响血压控制达标的相关因素.方法 对1012例来本院申请办理医疗保险高血压慢性病门诊的患者进行回顾性调查,分别记录患者的年龄、性别、患病年限、历史最高血压、当前血压、当前用药种类、随诊科室等情况.并统计达标率,分析在各科室或机构就诊患者的达标率;分析达标患者中各种药物的使用比例及联用情况;应用Logistic回归分析得出门诊高血压患者长期血压控制达标的影响因素.结果 患者平均年龄（66.2±10.9）岁,男357例,女655例,平均高血压患病时间（11.1±9.7）年,总体达标率34.4％,达标患者主要集中在心血管专科就诊,占71.2％;该人群中以钙离子拮抗剂（CCB）的使用率最高,1、2、3级高血压患者的使用率分别为62.1％、88.9％、80.8％;β受体阻滞剂（β-B）次之,分别为37.9％、58.3％、60.3％.1级血压达标患者51.7％单药治疗;随着血压水平升高,达标患者联合治疗比例增高：2、3级高血压患者分别为76.4％、85.9％;在2种药物组合中,最常被选用的联合是CCB和β-B,占44.4％,其次是CCB和血管紧张素受体拮抗剂（ARB）,占15.9％.Logistic回归分析显示：在心内科专科随诊、使用CCB是血压达标的独立促进因素（OR和P值分别为：14.49,0.019;1.95,0.005）.既往最高收缩压是影响达标的不利因素（OR =0.98,P=0.017）.结论 要高血压患者门诊药物治疗血压达标,应该定期在心血管专科门诊随诊以调整治疗方案,中度以上高血压患者应采取联合治疗,并应用以CCB为基础的联合治疗方案.     

护理教学中影响护生评判性思维能力因素分析及对策探讨

目的 探讨护理教学中影响护生评判性思维能力的因素及对策效果分析.方法 以我校在读的2009级全日制护理学专业的398名护生为研究对象,采用单因素Logistic回归分析、多因素Logistic回归分析方法,通过课堂气氛、实习等影响护理教学中护士评判性思维能力培养的最重要因素,展开针对性教学,探寻效果.结果 采用CTDI-CV进行评定,与培养实施前相比较,实施1年后评判性思维能力总分及各项指标均升高明显,差异具有,显著意义(P＜0.05).结论 通过有针对性的活跃课堂气氛,增加实习等实践机会,可有效提高护生的评判性思维能力.     

Impact of cardiovascular risk factor control on long-term cardiovascular and all-cause mortality in the general population

Purpose: In clinical trials, lowering cardiovascular risk factors (CVRFs) reduces cardiovascular (CV) morbidity and mortality. We assessed the impact of controlling CVRFs at baseline on long-term all-cause and CV mortality in the general population.

Methods: Analysis was based on the Third French MONICA population-based survey (1994–1997). Vital status was obtained 18 years after inclusion. Statistical analysis was based on Cox-modelling.

Results: About 3402 participants aged 35–64 were included and 569 (17%) presented with 2 or more uncontrolled CVRFs, 1194 (35%) had one uncontrolled CVRF, 770 (23%) had all CVRFs controlled under treatment (or were former smokers) and 869 (25%) exhibited no CVRF. During the follow-up, 389 deaths occurred (76 were due to CV causes). Considering all-cause mortality, the adjusted hazard ratios (aHR) for subjects with one uncontrolled CVRF and for those with two or more were 1.38 [1.03–1.83] (p?=?0.029) and 1.80 [1.33–2.43](p?aHR was 0.66 [0.44–0.98] (p?=?0.042). Considering CV mortality, aHRs for subjects presenting with one and two or more uncontrolled CVRF were 1.70 [0.84–3.42] (p?=?0.138) and 3.67 [1.85–7.29] (p?Conclusions: Failing to control CVRFs significantly increases long-term all-cause and CV mortality in the French general population.

• Key messages

• Only 30% of patients with cardiovascular risk factors were controlled.

• Failing to control cardiovascular risk factors significantly increased long-term cardiovascular and all-cause mortality.

• A residual risk for all-cause mortality remained even when patients were controlled.

     

BCEF0083对慢性应激抑郁大鼠海马脑源性神经营养因子含量的影响

目的：观察一种白僵菌代谢产物BCEF0083对慢性应激抑郁模型大鼠糖水消耗量和海马脑源性神经营养因子含量的影响.方法：实验于2003-10在安徽医科大学药理学教研室完成.①分组：选用雄性SD大鼠48只,随机分为6组：对照组、模型组、吗氯贝胺20 mg/kg组、BCEF0083 100,50,25 mg/kg组,每组8只.②模型制备：采用慢性不可预见性应激法造成大鼠抑郁模型.③给药：用药组灌胃给药,1次/d,共21 d,模型组及对照组灌胃蒸馏水,吗氯贝胺组灌胃剂量为20 mg/kg、BCEF0083大剂量组灌胃剂量为100 mg/kg,BCEF0083中剂量组灌胃剂量为50 mg/kg,BCEF0083小剂量组灌胃剂量为25 mg/kg.④用糖水消耗量法观测大鼠行为,用免疫组织化学测定海马脑源性神经营养因子的含量.结果：参加实验48只大鼠,全部进入结果分析.①在糖水消耗实验中：与对照组比较,模型组大鼠糖水消耗量降低（P＜0.01）;与模型组比较,BCEF0083 100 mg/kg组、BCEF0083 50 mg/kg组、BCEF0083 25mg/kg和吗氯贝胺20 mg/kg组均能增加慢性应激大鼠糖水消耗量（P＜0.01或P＜0.05）.②在BCEF0083对慢性应激大鼠海马脑源性神经营养因子含量的影响实验中：与对照组比较,模型组大鼠海马CA1,CA3,齿状回区的脑源性神经营养因子阳性神经元平均吸光度减小（P均＜0.01）;与模型组比较,BCEF0083 25 mg/kg组,50 mg/kg组和吗氯贝胺20 mg/kg组均能够不同程度分别增加慢性应激大鼠海马CA1,CA3,齿状回区的脑源性神经营养因子阳性神经元平均吸光度（P均＜0.01）;与对照组比较,模型组大鼠海马,CA3,齿状回区的脑源性神经营养因子阳性神经元面积百分比减小（P均＜0.01）;与模型组比较,BCEF0083 25 mg/kg,50 mg/kg均能不同程度分别增加慢性应激大鼠海马CA1,CA3,齿状回区的脑源性神经营养因子阳性神经元面积百分比（P＜0.01或P＜0.05）.结论：BCEF0083的抗抑郁作用可能与海马脑源性神经营养因子含量有关.     

BCEF0083对慢性应激抑郁大鼠海马脑源性神经营养因子含量的影响

目的:观察一种白僵菌代谢产物BCEF0083对慢性应激抑郁模型大鼠糖水消耗量和海马脑源性神经营养因子含量的影响。方法:实验于2003-10在安徽医科大学药理学教研室完成。①分组:选用雄性SD大鼠48只,随机分为6组:对照组、模型组、吗氯贝胺20mg/kg组、BCEF0083100,50,25mg/kg组,每组8只。②模型制备:采用慢性不可预见性应激法造成大鼠抑郁模型。③给药:用药组灌胃给药,1次/d,共21d,模型组及对照组灌胃蒸馏水,吗氯贝胺组灌胃剂量为20mg/kg、BCEF0083大剂量组灌胃剂量为100mg/kg,BCEF0083中剂量组灌胃剂量为50mg/kg,BCEF0083小剂量组灌胃剂量为25mg/kg。④用糖水消耗量法观测大鼠行为,用免疫组织化学测定海马脑源性神经营养因子的含量。结果:参加实验48只大鼠,全部进入结果分析。①在糖水消耗实验中:与对照组比较,模型组大鼠糖水消耗量降低(P<0.01);与模型组比较,BCEF0083100mg/kg组、BCEF008350mg/kg组、BCEF008325mg/kg和吗氯贝胺20mg/kg组均能增加慢性应激大鼠糖水消耗量(P<0.01或P<0.05)。②在BCEF0083对慢性应激大鼠海马脑源性神经营养因子含量的影响实验中:与对照组比较,模型组大鼠海马CA1,CA3,齿状回区的脑源性神经营养因子阳性神经元平均吸光度减小(P均<0.01);与模型组比较,BCEF008325mg/kg组,50mg/kg组和吗氯贝胺20mg/kg组均能够不同程度分别增加慢性应激大鼠海马CA1,CA3,齿状回区的脑源性神经营养因子阳性神经元平均吸光度(P均<0.01);与对照组比较,模型组大鼠海马,CA3,齿状回区的脑源性神经营养因子阳性神经元面积百分比减小(P均<0.01);与模型组比较,BCEF008325mg/kg,50mg/kg均能不同程度分别增加慢性应激大鼠海马CA1,CA3,齿状回区的脑源性神经营养因子阳性神经元面积百分比(P<0.01或P<0.05)。结论:BCEF0083的抗抑郁作用可能与海马脑源性神经营养因子含量有关。     

Impact of the factor V Leiden mutation on the outcome of pneumococcal pneumonia: a controlled laboratory study

Introduction  

Streptococcus (S.) pneumoniae is the most common cause of community-acquired pneumonia. The factor V Leiden (FVL) mutation results in resistance of activated FV to inactivation by activated protein C and thereby in a prothrombotic phenotype. Human heterozygous FVL carriers have been reported to be relatively protected against sepsis-related mortality. We here determined the effect of the FVL mutation on coagulation, inflammation, bacterial outgrowth and outcome in murine pneumococcal pneumonia.     

Impact of treatment with infliximab on anticyclic citrullinated peptide antibody and rheumatoid factor in patients with rheumatoid arthritis

OBJECTIVE: To investigate the impact of infliximab treatment on anticyclic citrullinated peptide (anti-CCP) antibody and rheumatoid factor (RF) levels in patients with rheumatoid arthritis (RA). METHODS: Sera from 33 RA patients receiving infliximab and disease modifying antirheumatic drugs were tested for anti-CCP antibody, IgA-, IgG- and IgM-RF using a commercially available semiquantitative ELISA at baseline, 30 and 54 weeks after treatment. RESULTS: The serum levels of anti-CCP antibody and IgA-RF decreased significantly after 30 weeks (P = 0.002 and 0.024); however, the decrease was not significant at week 54 (P = 0.147 and 0.207). The decrease in IgG-RF level was not significant at 30 and 54 weeks (P = 0.059 and 0.097). IgM-RF levels, however decreased significantly at 30 and 54 weeks (P = 0.002 and 0.004). A strong correlation between anti-CCP and IgA-, IgG- and IgM-RF was observed at baseline (r(s) = 0.48, 0.43, 0.65, P = < 0.05) and after infliximab treatment at 30 (r(s) = 0.45, 0.46, 0.62, P = < 0.05) and 54 (r(s) = 0.49, 0.45, 0.60, P = < 0.05) weeks. CONCLUSION: Treatment with infliximab results in decreased anti-CCP antibody and IgA-RF early in the course of therapy that is not sustained. IgM-RF declines and remains decreased for at least 54 weeks. Investigations in larger cohorts of RA patients (especially early RA) with longer follow-up are needed to assess the impact of specific therapeutic interventions on anti-CCP antibody and RF levels and the relationship of their levels to disease activity.